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Thursday, July 10, 2008

Dogs on Pills or humans are in fact using animal drugs

Dogs are a geneticist’s dream. Lab rats can be artificially induced to suffer certain problems — for example, electrically shocked to create a fearful state — whereas dogs are natural models, exhibiting anxiety, phobias and compulsions on their own. The canine genome, whose sequencing was recently completed, is considerably easier to analyze than the human one. The canine gene pool has been highly restricted and segregated during the creation of distinct dog breeds, much of which happened within the past 200 years. Members within a breed are highly similar genetically, making mutations that might cause behavior problems easier to spot. Purebred dogs are also excellent for testing theories about heritability. “There are fantastic genealogical resources that can connect dogs within a century for dozens of generations,” Hamilton says.

In certain breeds, almost all of the dogs alive today are descendants of a handful of popular sires that exemplified traits that breeders liked — for instance, a snowy white coat or exceptional herding ability. In selecting for these desired traits, however, the breeders sometimes inadvertently selected for the sires’ undesirable genetic mutations. This appears to be the case with canine compulsive disorder. A half-dozen or so breeds are predisposed to get it and in fact are susceptible to particular forms of the disorder — for example, German shepherds tend to tail-chase, while Doberman pinschers suck their flanks. Dodman and his colleagues are running genetic analyses of 146 Dobermans, more than half of them afflicted and the others not. His hunch is that a genetic glitch that leads to overactive glutamate receptors may increase susceptibility for developing compulsive behaviors. The same may be true for people. If this is correct, then it would ratify an approach that Dodman and a colleague have patented for treating both animal and human compulsive disorders with drugs that inhibit the glutamate receptors. Similar hunts are under way for the genetic underpinnings of what looks like psychotic rage in cocker spaniels and phobias in Australian shepherds, and those searches, too, may yield drug treatments for the canine and human versions of those problems.

Though certain dogs are probably genetically predisposed, environmental factors are clearly involved as well. “All of the animals I see that have O.C.D. are anxious individuals who’ve been in a rock-and-a-hard-place conflict situation in their lives which precipitates their condition,” Dodman says. Stressful situations in which an animal is repeatedly prevented from doing what it wants to do lead to anxiety, and anxiety can be relieved by indulging in a repeated behavior that long outlasts the original situation. That, it turned out, was exactly the case with Max. Though he lived a perfect dog’s life in California — plenty of love, company and exercise — Allan said that for most of the first year of his life, when he belonged to another owner, he was confined inside and all alone.

At end of the day that I visited Dodman, we sat watching video clips of dogs repetitively pacing, chasing shadows and snapping at nonexistent flies. Dodman, leaning back in his chair, launched into a story about a human obsessive-compulsive-disorder sufferer he had met — a man who repeatedly tugged at his beard. Dodman asked him if he had ever stopped, and the man said he did during a hitchhiking trip across Canada. Dodman thought he knew why: “He went back to being a human being. He was watching out for real dangers. He was trying to go to real places. He was concerned about his next meal. He was thinking about where he was going to sleep. And he wasn’t concerned about the stupid beard pulling, because now he had a real life. When did the problem start again? The minute he sat back in front of a flickering computer screen.”

Dodman’s theory, essentially, is that the causes of mood disorders and obsessions in humans and our pets aren’t so different — faulty genetics, dreary environments. Whether cubicle- or cage-bound, we get too little exercise; we don’t hunt, run or play enough to produce naturally mood-elevating neurochemicals. Strangely enough, I had already heard this theory — from a pharmaceutical company executive who, for obvious business reasons, didn’t want to be named. “All of the behavioral issues that we have created in ourselves, we are now creating in our pets because they live in the same unhealthy environments that we do,” he said. “That’s why there is a market for these drugs.”